The broad objective of this proposal is to identify mechanisms of hematopoietic stem cell damage occurring after cancer chemotherapy use. We intend to determine if this damage is lessened (or exacerbated) by use of cytokines with chemotherapy and to discover ways to avoid such damage. Changes in primitive hematopoietic stem cell (PHSC) function and numbers will be assessed. Changes in PHSC cycling will also be examined to determine if such changes are, in part, accountable for increased PHSC vulnerability after chemotherapy and subsequent PHSC exhaustion of dysfunction. The hypothesis that chemotherapy alters normal physiologic growth responsiveness will also be tested.